ساخت و مشخصه‌يابي نانوليپوزوم‌هاي بارگذاري شده با سانيتينيب و هدفمند شده با آنتي‌بادي مونوكلونال تراستوزومب و بررسي خواص ضد سرطاني آن‌ها

Synthesis an‎d characterization of sunitinib loaded & trastuzumab functionalized nanoliposome an‎d investigation of their anticancer activity

زيست فناوري

Breast cancer is one of the most preva‎lent an‎d lethal malignancies among women an‎d remains a major global health challenge. Tyrosine kinase inhibitors (particularly sunitinib) are among the key therapeutic agents used in cancer treatment; however, limitations such as high systemic toxicity, insufficient targeting efficiency, an‎d the inability to simultaneously monitor therapeutic response continue to reduce their overall effectiveness. The development of advanced nanosystems offers not only enhanced selec‎tive cellular uptake an‎d reduced drug related side effects but also the potential for real time tumor tracking. Accordingly, in the present study, a novel multifunctional platform based on sunitinib loaded nanoliposomes modified with trastuzumab an‎d integrated with carbon dots was designed an‎d developed to enable controlled an‎d targeted drug release alongside dual fluorescence an‎d magnetic resonance imaging for the treatment of HER2 positive breast cancer.The nanoliposomes synthesized via the thin film hydration method exhibited an average size of 130 nm an‎d a zeta potential of −15 mV, which decreased to 114 nm an‎d −11 mV following covalent conjugation of the antibody, confirming favorable colloidal stability. MTT assays on HER2 positive breast cancer cells an‎d human fibroblasts demonstrated that empty liposomal nanoparticles were the safest formulation across all concentrations, maintaining cell viability above 95%. In contrast, the combined LPSTC formulation (liposome containing drug, antibody, an‎d magnetic carbon dots) exhibited the highest cytotoxicity at elevated concentrations, reducing viability to below 20% in cancer cells. Nevertheless, targeted sunitinib loaded formulations induced significantly lower toxicity in healthy fibroblasts compared to free drug, preserving viability above 80%, thereby confirming their high biocompatibility an‎d clinical potential. RT PCR analysis revealed that the LPSTC formulation induced the strongest apoptotic response in SK Br 3 cells, characterized by marked upregulation of Caspase 3, Caspase 8, an‎d Apaf 1, along with significant downregulation of VEGF C. Consistently, ELISA an‎d flow cytometry results demonstrated that LPSTC markedly increased Caspase 3 an‎d Caspase 7 activity an‎d induced the highest level of apoptosis (87.2% total; 64.1% late an‎d 23.1% early) without notable necrosis, outperforming free sunitinib an‎d trastuzumab. CAM assay results further confirmed that LPSTC exerted the strongest anti angiogenic effect, producing the greatest reduction in vascular density compared to other groups. Finally, ex vivo fluorescence imaging an‎d both ex vivo an‎d in vivo MRI demonstrated that liposomal magnetic carbon dots not only produced a substantial enhancement in T1 signal intensity within the tumor region but also exhibited targeted accumulation an‎d preserved optical properties within the complex biological environment, highlighting their potential as versatile multimodal imaging agents for cancer diagnosis an‎d therapy.

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